...
首页> 外文期刊>Oncogene >Downregulation of uPA inhibits migration and PI3k|[sol]|Akt signaling in glioblastoma cells
【24h】

Downregulation of uPA inhibits migration and PI3k|[sol]|Akt signaling in glioblastoma cells

机译:uPA的下调抑制胶质母细胞瘤细胞的迁移和PI3k | [sol] | Akt信号传导

获取原文
   

获取外文期刊封面封底 >>

       

摘要

The ability of glioma cells to migrate great distances from a primary tumor mass is the primary cause of tumor recurrence. The urokinase-type plasminogen activator (uPA) is a serine protease that can initiate proteolytic cascades, which result in remodeling of extracellular matrix and basement membrane, allowing cells to move across and through these barriers. The binding between uPA and its receptor uPAR also mediates several signaling events that seem to contribute to the evolution of a migratory phenotype. In this study, we determined how the downregulation of uPA affects the signaling pathways leading to cell migration. Stably transfecting human glioblastoma cells with antisense uPA decreased the amount of cell-bound uPA and disrupted actin cytoskeleton formation and cell migration. The phosphatidylinositol 3-kinase (PI3k) and Akt signaling pathway has been suggested to mediate migration in various cancer cells. The antisense-uPA clones also had less phosphorylated PI3k and Akt than control cells, a finding associated with decreased cell migration, G2/M-phase arrest, and decreased clonogenic survival. Decreased activation of PI3k and the antiapoptotic factor Akt was not sufficient to induce apoptosis in the antisense-uPA clones, but staurosporine sensitized them to apoptosis to a greater extent than control cells. These results indicate that PI3k/Akt pathway is involved in the signaling cascade required to induce cell migration and that uPA has a direct role in regulating migration.
机译:胶质瘤细胞从原发肿瘤块迁移远距离的能力是肿瘤复发的主要原因。尿激酶型纤溶酶原激活剂(uPA)是一种丝氨酸蛋白酶,可以启动蛋白水解级联反应,从而导致细胞外基质和基底膜的重塑,从而使细胞能够穿越并穿过这些屏障。 uPA及其受体uPAR之间的结合也介导了一些信号传递事件,这些信号事件似乎有助于迁移表型的演变。在这项研究中,我们确定了uPA的下调如何影响导致细胞迁移的信号通路。用反义uPA稳定转染人胶质母细胞瘤细胞减少了细胞结合uPA的量,并破坏了肌动蛋白的细胞骨架形成和细胞迁移。磷脂酰肌醇3-激酶(PI3k)和Akt信号通路已被提出来介导各种癌细胞中的迁移。反义-uPA克隆的PI3k和Akt磷酸化程度也低于对照细胞,这一发现与细胞迁移减少,G2 / M期阻滞和克隆形成存活率降低有关。 PI3k和抗凋亡因子Akt的激活减少不足以诱导反义uPA克隆中的凋亡,但是星形孢菌素比对照细胞更敏感地诱导它们凋亡。这些结果表明PI3k / Akt途径参与诱导细胞迁移所需的信号级联反应,并且uPA在调节迁移中具有直接作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号